A soluble form of lymphocyte activation gene-3 (IMP321) induces activation of a large range of human effector cytotoxic cells

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Chrystelle Brignone - , Immutep S.A. (Author)
  • Caroline Grygar - , Immutep S.A. (Author)
  • Manon Marcu - , Immutep S.A. (Author)
  • Knut Schäkel - , Department of Dermatology, Institute for Immunology (Author)
  • Frédéric Triebel - , Immutep S.A. (Author)

Abstract

The principal antitumor immune response is mediated through the activation of type 1 cytotoxic (Tc1) CD8 T cells, NK cells, and monocytes/macrophages. In this study, we investigated the potency of a clinical-grade soluble form of lymphocyte activation gene-3 protein (IMP321), a physiological high-affinity MHC class II binder, at inducing in PBMCs an appropriate cytotoxic-type response in short-term ex vivo assays. We found that IMP321 binds to a minority (<10%) of MHC class II + cells in PBMCs, including all myeloid dendritic cells, and a small fraction of monocytes. Four hours after addition of IMP321 to PBMCs, these myeloid cells produce TNF-α and CCL4 as determined by intracellular staining. At 18 h, 1% of CD8+ T cells and 3.7% NK cells produce Tc1 cytokines such as IFN-γ and/or TNF-α (mean values from 60 blood donors). Similar induction was observed in metastatic cancer patient PBMCs, but the values were lower for the NK cell subset. Early APC activation by IMP321 is needed for this Tc1-type activation because pure sorted CD8 + T cells could not be activated by IMP321. Only Ag-experienced, fully differentiated granzyme + CD8 T cells (effector and effector memory but not naive or central memory T cells) are induced by IMP321 to full Tc1 activation. In contrast to IMP321, TLR1-9 agonists induce IL-10 and are therefore unable to induce this Tc1 IFN-γ+ response. Thus, IMP321 has many properties that confirm its potential to be a new class of immunopotentiator in cancer patients.

Details

Original languageEnglish
Pages (from-to)4202-4211
Number of pages10
JournalJournal of Immunology
Volume179
Issue number6
Publication statusPublished - 15 Sept 2007
Peer-reviewedYes

External IDs

PubMed 17785860

Keywords

Sustainable Development Goals

ASJC Scopus subject areas